We propose to investigate alternative methods of ovulation induction in infertile women with two common disorders of ovarian follicular development and atresia, polycystic ovarian syndrome (PCO) and "premature ovarian failure" (POF). In women with PCO, we shall attempt to interrupt the cycle of chronic anovulation and induce follicular maturation by 1) reducing peripheral estrogen production in obese individuals through weight reduction, 2) increasing FSH concentrations by administering exogenous pituitary FSH, and 3) decreasing LH Levels by giving a dopamine agonist, 2 alpha-bromoergocriptine. In separate experiments we shall investigate the possible role of the ACTH-like peptides, alpha-melanocyte stimulating hormone (alpha-MSH) and beta-endorphin, in initiating or modulating excessive androgen secretion by the ovary and/or adrenal gland. In women with POF, specific diagnostic techniques will be utilized in an effort to ascertain the etiology and to determine which individuals have remaining viable ovarian follicles. Emphasis will be placed on identifying women with either autoimmune dysfunction involving the ovary or altered molecular forms of circulating gonadotropins. In women with autoimmune disorders and functioning follicles, definitive treatment with corticosteroids and/or plasmapheresis will be initiated in an attempt to halt follicular destruction and allow normal follicular maturation. In individuals with evidence of abnormal forms of gonadotropins and viable follicles, exogenous human menopausal and chorionic gonadotropin will be administered to induce ovulation. Together, these studies will provide an important link in our understanding of follicular maturation and chronic anovulation in infertile women. The proposed therapeutic measures are based on more precise knowledge of the pathophysiology of these ovarian disorders than has been available previously.